Document Detail


Zinc stabilizes adenomatous polyposis coli (APC) protein levels and induces cell cycle arrest in colon cancer cells.
MedLine Citation:
PMID:  15368361     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the present study, we investigated the mechanisms by which zinc causes growth arrest in colon cancer cells. The results suggest that zinc treatment stabilizes the levels of the wild-type adenomatous polyposis coli (APC) protein at the post-translational level since the APC mRNA levels and the promoter activity of the APC gene were decreased in HCT-116 cells (which express the wild-type APC gene) after treatment with ZnCl2. Increased levels of wild-type but not truncated APC proteins were required for the ZnCl2-mediated G2/M phase arrest in different colon cancer cell lines. We further tested whether serum-stimulation, which induces cell cycle arrest in the S phase, can relieve ZnCl2-induced G2/M phase arrest of HCT-116 cells. Results showed that in the HCT-116 cells pretreated with ZnCl2, the serum-stimulation neither changed the distribution of G2/M phase arrested cells nor the increased levels of APC protein. The G2/M phase arrest correlated with retarded growth of HCT-116 cells. To further establish that wild-type APC protein plays a role in ZnCl2-induced G2/M arrest, we treated SW480 colon cancer cells that express truncated APC protein. We found that ZnCl2 treatment did not induce G2/M phase arrest in SW480 cells; however, the cell growth was retarded due to the loss of E-cadherin and alpha-tubulin levels. These results suggest that ZnCl2 inhibits the proliferation of colon cancer cells (which carry the wild-type APC gene) through stabilization of the APC protein and cell cycle arrest in the G2/M phase. On the other hand, ZnCl2 inhibits the proliferation of colon cancer cells (which carry the mutant APC gene) by disrupting cellular attachment and microtubule stability.
Authors:
Aruna S Jaiswal; Satya Narayan
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  93     ISSN:  0730-2312     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-09-15     Completed Date:  2005-01-06     Revised Date:  2013-02-20    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  345-57     Citation Subset:  IM    
Copyright Information:
Copyright 2004 Wiley-Liss, Inc.
Affiliation:
Department of Anatomy and Cell Biology and UF Shands Cancer Center, College of Medicine, University of Florida, Gainesville, Florida 32610, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenomatous Polyposis Coli Protein / genetics,  metabolism*
Cadherins / metabolism
Caspase 3
Caspases / metabolism
Cell Cycle / drug effects*
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Shape / drug effects
Chlorides / pharmacology*
Colonic Neoplasms / metabolism*,  pathology*
Cyclins / metabolism
Cytoskeletal Proteins / metabolism
G2 Phase / drug effects
Humans
Mitosis / drug effects
RNA, Messenger / genetics,  metabolism
Serum
Signal Transduction
Trans-Activators / metabolism
Zinc Compounds / pharmacology*
beta Catenin
Grant Support
ID/Acronym/Agency:
R01 CA077721/CA/NCI NIH HHS; R01 CA097031/CA/NCI NIH HHS; R01-CA77721/CA/NCI NIH HHS; R01-CA97031/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Adenomatous Polyposis Coli Protein; 0/CTNNB1 protein, human; 0/Cadherins; 0/Chlorides; 0/Cyclins; 0/Cytoskeletal Proteins; 0/RNA, Messenger; 0/Trans-Activators; 0/Zinc Compounds; 0/beta Catenin; 86Q357L16B/zinc chloride; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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